The goal of the Microbial Ecology and Theory of Animals Center in Systems Biology (META CSB) at the University of Oregon is to create the foundation for a new field of host-microbe Systems Biology. Our Center will innovate the tools, experimental approaches, best practices, analytical frameworks, and conceptual models required to describe how host-microbe systems organize, how hosts and microbes interact dynamically through space and time, and how these systems evolve. We will focus on the complex host associated microbial system of the vertebrate intestine and will study both sides of the interaction, characterizing the microbial communities as well as the host responses in toto with respect to their components, dynamics, and the evolutionary forces driving their interactions. We will use two fish models, zebrafish and stickleback, to perform well-controlled, manipulative experiments that mirror host-microbe interactions in humans. Our investigations will combine the theoretical rigor of community ecology and population biology with the experimental elegance of our gnotobiotic fish models, whose bacterial communities can be entirely defined. We will exploit innovations in sequencing technology and live imaging to create comprehensive large-scale datasets describing the membership and dynamics of host-associated microbial communities and corresponding host responses. We will innovate applications of sampling theory, spatial biodiversity theory, and probabilistic models to analyze our data and deduce system-level properties about host-microbe system assembly, dynamics, and evolution. The knowledge and approaches we develop for host-microbe Systems Biology will be directly applicable to studies of microbial communities associated with humans, such as the Human Microbiome Project, and will revolutionize the understanding of numerous diseases including inflammatory bowel diseases, diabetes, cancers, asthma, and autism. Our innovative and integrated approaches to scientific inquiry, education, and outreach will create a fertile training environment for a new and diverse generation of host-microbe System Biologists.